Extraction of materials from liquids

ABSTRACT

An apparatus for extracting a material from a liquid includes a concentration stage having a filter, a first path from the filter, and a second path from the filter. Under this configuration, the concentration stage accepts an initial liquid volume. A first liquid not having material collected by the filter is passed along the first path, and concentrated liquid having material therein, which is entrapped by the filter, is directed to the second path. The apparatus also includes an aerosolizing stage coupled to the concentration stage that converts the concentrated liquid into an aerosol and a drying stage that dries the aerosol such that material extracted from the aerosol onto a material substrate.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/545,125, filed Aug. 20, 2019, entitled EXTRACTION OF MATERIALS FROMLIQUIDS, now allowed, which claims the benefit of U.S. ProvisionalPatent Application Ser. No. 62/720,211, filed Aug. 21, 2018, having thetitle EXTRACTION OF MATERIAL FROM A LIQUID, the disclosure of which ishereby incorporated by reference.

BACKGROUND

The present disclosure relates generally to the extraction of a materialfrom a liquid, and more particularly to the concentration,aerosolization, collection, detection, analysis, or combinationsthereof, of a liquid sample comprising the material.

A variety of liquids, including water, destined for consumption orinjection must be monitored and controlled for the presence of harmfulcontaminants, such as bacteria, fungi, and mold. Furthermore, liquidsused, for example, in laboratory testing, manufacturing, and other typesof facilities may also need to be monitored to detect the presence ofsuch contaminants.

BRIEF SUMMARY

In accordance with an aspect of the present disclosure, an apparatus forextracting a material from a liquid comprises a concentration stage, anaerosolizing stage, and a drying stage. The concentration stage acceptsan initial liquid volume, where the initial liquid volume has an initialconcentration of a material. Moreover, the concentration stage comprisesa filter, a first path from the filter, and a second path from thefilter. The filter accepts the initial liquid volume and collects thematerial from the initial liquid volume. More particularly, the filterproduces a permeate that is substantially devoid of the collectedmaterial, and the filter produces a retentate that has a higherconcentration of the material than the initial concentration. In thisregard, the first path from the filter defines a conduit for thepermeate, and the second path from the filter defines a conduit for theretentate. The aerosolizing stage is coupled to the second path andconverts the retentate into an aerosol. The drying stage dries theaerosol to extract the material and collects the extracted material ontoa material substrate.

In example embodiments, the permeate represents a first portion of theliquid volume introduced to the concentration stage. The permeate, whichdoes not have material collected by the filter, is passed along thefirst path. Correspondingly, the retentate represents a second portionof the liquid volume introduced to the concentration stage. Theretentate defines a concentrated liquid having material therein, whichis entrapped by the filter, and is directed to the second path. In someembodiments, the filter is a tangential flow filter.

In accordance with another aspect of the present disclosure, a processfor extracting materials from liquids is provided. The process comprisesintroducing an initial liquid volume into a concentration stage, theinitial liquid volume having an initial concentration of a material. Theprocess also comprises directing the initial liquid volume into a filterfor entrapping the material to produce a concentrated liquid having ahigher concentration of the material than the initial concentration. Theprocess further comprises directing the concentrated liquid out of theconcentration stage. The process still further comprises introducing aportion of the concentrated liquid into a nebulizer to produceaerosolized liquid droplets and heating the aerosolized liquid dropletsin a drying chamber to extract the material from the liquid droplets.

According to yet further aspects of the present disclosure, an apparatusfor extracting materials from liquids, comprises a concentration stage,an aerosolizing stage, a drying stage, a controller, and an analyzer.The concentration stage accepts an initial liquid volume having aninitial concentration of a material. Moreover, the concentration stagecomprises a filter, a permeate path, and a retentate path. The filteraccepts the initial liquid volume, collects the material from theinitial liquid volume, produces a permeate that is substantially devoidof the collected material, and produces a retentate having a higherconcentration of the material than the initial concentration. Thepermeate path comprises a conduit having a flow meter, and a permeatecontrol valve there-along. Moreover, the permeate path directs thepermeate from the filter. The retentate path comprises a conduit havinga retentate control valve there-along. The retentate path directs theretentate from the filter. The aerosolizing stage is coupled to theretentate path and converts the retentate into an aerosol. The dryingstage dries the aerosol to extract the material, wherein the extractedmaterial is collected onto a material substrate. The controller iscoupled to the concentration stage, and to the aerosolizing stage,wherein the controller automates liquid sample collection. The analyzeris coupled to the controller, which operates in parallel with the liquidsample collection to analyze the material collected onto the materialsubstrate.

BRIEF DESCRIPTION OF THE DRAWINGS

The following detailed description of various aspects of the presentdisclosure may be best understood when read in conjunction with thefollowing drawings, where like structure is indicated with likereference numerals, and in which:

FIG. 1 illustrates a block diagram of a system for extracting andanalyzing a material from a liquid sample, in accordance with variousaspects of the present disclosure;

FIG. 2 illustrates a block diagram of an apparatus that extractsmaterials from liquids, in accordance with various aspects of thepresent disclosure;

FIG. 3 is a schematic diagram of a system for extracting a material froma liquid sample, in accordance with various aspects of the presentdisclosure;

FIG. 4 is a schematic diagram of a liquid concentrator, in accordancewith various aspects of the present disclosure;

FIG. 5 is a flowchart illustrating a process for extracting a materialfrom a liquid sample, in accordance with various aspects of the presentdisclosure; and

FIG. 6 is a block diagram of another example apparatus for extractingmaterials from liquids, according to aspects herein.

DETAILED DESCRIPTION

Liquids (including, but not limited to water) may be utilized for tasksthat can include consumption, injection, food preparation, industrialprocesses, pharmaceutical processes, etc. However, such liquids maycarry harmful microorganisms such as bacteria, fungi and mold. Dependingon the use of the liquid, an acceptable concentration level may beestablished. For instance, in an example implementation, an acceptableconcentration of microorganisms may be less than 1 cell per milliliter(mL). In addition, the species and/or strains of microorganisms in theliquid may need to be determined. For instance, depending upon the useof the liquid, different species of microorganism can have significantlydifferent impacts, including different health impacts. Accordingly,aspects herein concentrate and collect liquids. The concentrated andcollected liquid can then be monitored for the presence of harmfulmicroorganisms.

Responsive to the detection of harmful microorganisms, workflows canthus be controlled, such as to stop industrial processes, triggeralarms, issue reports, flag detection, identify detected species,identify detected strains, identify detected concentrations, performclassification and report results, etc., as described more fully herein.

Moreover, aspects herein address issues with monitoring liquids with lowliquid concentrations by processing a sufficient volume of liquid, suchas to ensure the statistical accuracy of detection or quantification,minimize the loss of particulates (e.g., cellular material), leave thecellular material in a format compatible with follow-on analysis, etc.

Aspects of the present disclosure are directed to methods, apparatus,and systems for automatically concentrating, aerosolizing, drying,collecting, monitoring, combinations thereof, etc., particulates (e.g.,cellular material) that are suspended in a liquid source. Moreparticularly, such approaches accept an initial liquid volume and applyfiltration to generate a concentrate (a reduced liquid volume thatcontains the cellular material at a higher concentration). Aspectsherein also aerosolize that concentrate (e.g., through a nebulizer) anddry the aerosol to separate the material (e.g., cells) from the liquid.Moreover, in certain embodiments, the concentrate is monitored, e.g., bytransferring the concentrate to an analyzer, or by monitoring theconcentrate in the same apparatus that dries the aerosol. Notably, theapproaches herein yield a decrease in time to result, a decrease inlabor investment, or a combination thereof.

Yet further, certain aspects of the present disclosure provide for acontrol scheme, which may be executed by a computer or other processorrunning executable computer code. In this regard, the computer code isread out and is executed by the system to automate the processesdescribed more fully herein, e.g., to automatically concentrate,aerosolize, dry, collect, monitor, analyze, control, combinationsthereof, etc., cellular material that is suspended in a liquid source.

According to further aspects of the present disclosure, an apparatus andprocess are provided to extract materials from liquids. A liquid ofinterest, at a first, lower concentration of material, is reduced to aconcentrated liquid comprising a smaller liquid volume containingmaterial at a higher concentration. The concentrated liquid is thenaerosolized and at least partially dried to separate the material fromthe liquid. The liquid may comprise, for example, water. In otherexamples, the liquid may include, but is not limited to, a smallmolecule formulation. A small molecule formulation includes, forexample, an aqueous sample that includes other components such as salts,surfactants, antiseptic molecules, etc. Other aqueous and non-aqueousliquids can include methanol, ethanol, wine, beer, liquor, organicsolvents, milk, etc.

The material to be extracted from the liquid may comprise, for example,particulates such as one or more microorganisms, including bacteria,protozoa, fungi, algae, viruses, and fragments or portions thereof. Thematerial may also comprise nucleic acids, proteins, polymers, and otherbiological and non-biological particles and contaminants. The materialmay be collected and subjected to additional analysis to detect andidentify the presence of microorganisms and/or other types of particles.

Referring now to the drawings and in particular to FIG. 1, a blockdiagram illustrates a system 100 for collecting, concentrating, andmonitoring for materials suspended in a liquid, according to variousaspects of the present disclosure. In practical applications, liquid isprovided from a liquid source 102. As will be described in greaterdetail herein, the liquid source 102 can comprise water collected from awater supply, a liquid sample (water or otherwise) collected from animpactor, a liquid (water or otherwise) extracted from a manufacturingor pharmaceutical process, etc.

A concentration and aerosolizing apparatus 104 receives liquid from theliquid source 102. In this regard, the concentration and aerosolizingapparatus 104 extracts materials from liquids, e.g., to prepare a samplefor monitoring or other analysis. This may comprise collecting,concentrating, aerosolizing, drying, incubating, combinations thereof,or other processing steps necessary to prepare a sample for subsequentanalysis. For instance, in an example implementation, the concentrationand aerosolizing apparatus 104 accepts an initial liquid volume from theliquid source 102, and filters material from the initial liquid volume,producing a permeate that is substantially devoid of the collectedmaterial, and producing a retentate that has a higher concentration ofthe material than the initial concentration. The retentate is directedto an aerosolizing stage that converts the retentate into an aerosol,and a drying stage dries the aerosol to extract the material, e.g., ontoa material substrate. Example implementations of concentration,aerosolizing, drying, combinations thereof, etc., are described ingreater detail herein, e.g., with regard to FIGS. 2-6.

An optional drain 106 can be provided in certain embodiments, and isused to redirect liquid, e.g., water, a carrier, residual, waste, orother fluid not necessary for subsequent analysis, to a suitabledestination, e.g., for disposal, recycling, or other use.

An analyzer 108 accepts the material (or a sample thereof), collected bythe concentration and aerosolizing apparatus 104 to perform a desiredanalysis. Here, the analyzer 108 can utilize fluorescence, RamanSpectroscopy, imaging, a microscope, chemistry, other techniques,combinations thereof, etc. to monitor the collected material, analyzethe material to provide an indication of the contents of the sample,combinations thereof, etc.

An output 110 provides a result from the analyzer 108. Here, the output110 can be an alarm, a message, a report, combinations thereof, etc.Moreover, the output 110 can be expressed in different manifestations.For instance, the output 110 can be based upon a detected broadclassification—e.g., the sample includes biological material. The output110 can be based upon a computed statistical probability that exceeds athreshold. For instance, there is a 90% likelihood that the sampleincludes a biological material. In other examples, the output 110 can bebased upon a detection exceeding a predetermined criterion or set ofcriteria, e.g., material exceeds a concentration of x part(s) pervolume, e.g., 1 part per milliliter (mL); biological material exceeds 1cell per milliliter (mL) regardless of total material content), etc.Moreover, the output 110 can include precise species/strainidentification or classification, including the detection of multiplespecies. The output 100 can also comprise an email, a text message,other alert, a workflow, e.g., to start or stop a process, a command tostart, stop, continue, etc., an industrial machine/process based uponthe monitoring results, a command to start, stop, continue, etc., apharmaceutical machine/process based upon the monitoring results etc.Yet further, any combination of the above can be implemented.

A controller 112 couples to the concentration and aerosolizing system104 and the analyzer 108, as shown. The controller 112 provides thecontrol, timing, and synchronization required for themonitoring/analysis of liquid samples. For instance, the controller 112can control the concentration and aerosolizing system 104 to collect aliquid sample and pass the sample to the analyzer 108 for subsequentanalysis. The controller 112 can also interface with externalelectronics, e.g., to carry out processes defined by the output 110,e.g., to control downstream machines/processes, send alerts, etc.

Referring to FIG. 2, a block diagram 200 illustrates an apparatus forextracting a material from a liquid sample, in accordance with variousaspects of the present disclosure. The block diagram 200 furtherillustrates example components capable of implementing the concentrationand aerosolizing apparatus 104 of FIG. 1.

As will be described in greater detail herein, an apparatus forextracting a material from a liquid (e.g., concentration andaerosolizing apparatus) comprises in general, a concentration stage, anaerosolizing stage, and a drying stage. The apparatus can also includeadditional components that each may support one or more of functions,such as concentration, storing, aerosolizing, and drying, etc.

As illustrated, an example concentration and aerosolizing apparatus 104includes an optional input stage 202 that serves as an input forobtaining a liquid sample.

A concentration stage 204 is coupled to the input stage 202 and isoperatively configured to receive the obtained liquid sample from theinput stage 202. The concentration stage 204 converts a relatively largevolume of liquid having a low concentration of interest, to a relativelylower volume of liquid with a relatively higher concentration ofinterest.

In general, the concentration stage 204 can comprise one or more controlvalves that define paths through the apparatus. The control valves arecontrolled (e.g., by the controller 112 of FIG. 1) to control a flow ofthe liquid through the concentration and aerosolizing apparatus 104. Theconcentration stage 204 may also comprise a pressure transmitter orregulator that controls a pressure of the liquid as it is introducedinto the system. Here, the pressure regulator may be located upstream ofa first control valve. As used herein, the term “upstream” refers to apoint located toward a sample introduction port or otherwise opposite aflow direction, and the term “downstream” refers to a point locatedtoward an exit, such as a drain line, or otherwise with a flowdirection.

As will be described in greater detail herein, in an example embodiment,the concentration stage 204 comprises a tangential flow filter 204A, afirst path 204B from the tangential flow filter 204A, and a second path204C from the tangential flow filter 204A. More particularly, thetangential flow filter 204A accepts an initial liquid volume (e.g., fromthe input stage 202). The tangential flow filter 204 further collectsmaterial from the initial liquid volume, produces a permeate that issubstantially devoid of the collected material, and produces a retentatethat has a higher concentration of the material than the initialconcentration.

A first portion of the liquid volume that is introduced to theconcentration stage 204, which does not have material collected by thetangential flow filter (the permeate), is directed along the first path204B, e.g., to drain 106. Correspondingly, a second portion of theliquid volume introduced to the concentration stage 204, defining aconcentrated liquid having material therein, which is entrapped by thetangential flow filter (the retentate), is directed along the secondpath 204C.

An optional reservoir 206 can receive the output of the concentrationstage 204, e.g., to collect the retentate directed along the second path204C. The reservoir 206 serves as a holding area until a suitable timefor subsequent analysis. For instance, the reservoir 206 may accumulateliquid until such time as a suitable concentration is built up, untilsuch time as a predetermined cycle has run, until such time as apredetermined amount of liquid has built up, until a downstreamcomponent requests liquid, until a trigger occurs requiring a sampleanalysis, or based upon any other factor(s), e.g., that can beautomated, e.g., based upon computer control.

An aerosolizing stage 208 coupled to the second path 204C receivesliquid (e.g., optionally from the reservoir 206 where provided) andconverts the retentate into an aerosol, e.g., using a nebulizer or othersuitable hardware.

A drying stage 210 dries the aerosolize (representing an aerosolizedsample), which extracts the material from any remaining liquid content.In an example embodiment, the drying stage 210 dries the aerosol suchthat material extracted from the aerosol is collected onto a materialsubstrate.

An optional collection stage 212 receives the dried sample and can thusprovide a concentrated and prepared sample for subsequent analysis. Inthis regard, the sample can be provided on a suitable material substrate214. The sample substrate 214 is a substrate that is compatible with theassociated analysis technology, storage requirements, collectionrequirements, combinations thereof, etc.

An optional controller 216 (e.g., in addition to, or in lieu of thecontroller 112, FIG. 1) can be provided to automate or semi-automatematerial concentration, aerosolizing, drying, collecting, combinationsthereof, etc. As illustrated, the controller 216 is communicably coupledto one or more stages of the concentration and aerosolizing apparatus104, e.g., the input stage 202, concentration stage 204, reservoir 206,aerosolizing stage 208, drying stage 210, collection stage 212, etc.Here, the controller 216 can communicate with controllable valves,meters, sensors, or other fixtures in order to implement componentcontrol, timing, etc., examples of which are described more fullyherein.

Referring to FIG. 3, a schematic diagram of an apparatus 300 forextracting a material from a liquid sample is illustrated, in accordancewith various aspects of the present disclosure. In this regard, thesystem 300 is an example of concentration and aerosolizing apparatus 104of FIG. 1 and/or FIG. 2. As such, like elements between FIG. 2 and FIG.3 are illustrated with corresponding reference numerals 100 higher inFIG. 3 than the counterpart in FIG. 2.

The apparatus 300 accepts a volume of liquid and extracts a sampletherefrom. In this regard, the system 300 is also referred to herein asa liquid sample adapter (LSA).

As an overview, in a manner analogous to FIG. 2, the LSA comprises aninput stage 302 that provides a liquid to a concentration stage 304. Theoutput of the concentration stage 304 is stored in a reservoir 306. Anaerosolizing stage 308 pulls liquid from the reservoir 306 andaerosolizes the liquid to define a sample. The sample is dried by adrying stage 310 and is accumulated at a collection stage 312 on amaterial substrate 314 for subsequent analysis.

In more specific detail, a liquid source 320 (e.g. analogous to theliquid source 102 of FIG. 1) provides a source of liquid for evaluation.In an example embodiment, the liquid source 320 can comprise a clientwater system, supply of liquid in a manufacturing, industrial, orpharmaceutical application, supply from a sample collector, etc. In thisregard, the liquid source 320 can provide the liquid to the system 300via various valves, pipes, tubing, conduit, or other appropriateconveyance components (collectively supply fixtures 322).

The input stage 302 accepts an initial volume of liquid from the liquidsource 320. In this regard, the system 300 can include input fixtures324 (e.g., piping, valves, fittings, pumps, check valves, etc.) tocouple the liquid from the liquid source 320 to the system 300. In anexample implementation, the input stage 302, e.g., via a liquidintroduction port and an input control valve, accepts a volume ofliquid, on the order of 1 to 100 liters, for processing. In an exampleimplementation, this “initial volume” is introduced at an elevatedpressure that is regulated by the LSA to be in the range of 15 to 25pounds per square inch (PSI). This controlled but elevated pressureprovides the motive force for the concentration stage 304. The LSAregulates the pressure so that the liquid source 320 can have variablecharacteristics, including a wide range of pressures, the liquid source320 can be static or flowing, etc.

A first control valve 326 controls the flow of liquid from the inputstage 302 to the concentration stage 304. An optional second controlvalve 328 can be opened to divert liquid to a suitable drain, e.g., viaa suitable drainage line 330.

In the concentration stage 304, the initial volume is directed via thefirst control valve 326 into a tangential flow filter 332. A flow rateinto the tangential flow filter 332 is controlled by the regulatedpressure of the system 300. The tangential flow filter 332 is selectedso that liquid passes through a first path, designated a permeate path334, as the “permeate”, but cellular material is retained inside thetangential flow filter 332, in the “retentate” volume, which willsubsequently be expelled from the tangential flow filter 332 via asecond path, designated a retentate path 336, as described more fullyherein.

In an example embodiment, the permeate path 334 includes a flow meter340 and a permeate control valve 342. Correspondingly, the retentatepath 336 includes a retentate control valve 338. In this manner, thepermeate control valve 342 is open and the retentate control valve 338is closed during collection. In another example, the retentate controlvalve 338 comprises a closed position, an open position, and an open todrain position, which provides for a drain path to prime and clean thetangential flow filter 332 by directing fluid to a drain line, bypassingthe aerosolizing stage 308. For instance, the drain path can direct theliquid through the concentration stage and into the drain line withoutentering the aerosolizing stage 308.

As illustrated, as the initial volume is passing through the tangentialflow filter 332, a retentate control valve 338 blocks the retentateoutflow, leading to an accumulation of cellular material inside thetangential flow filter 332 in a “concentrated liquid”. The concentratedliquid has a higher cell density (cells per unit volume) than theinitial volume.

The remaining liquid, e.g., the non-concentrated liquid, is directed outthe permeate path 334 and passes through a flow meter 340 to meter theamount of liquid input into the system. Here, a permeate control valve342 is open so that the non-concentrated liquid can be disposed, e.g.,via the drainage line 330.

Once the initial volume has passed across the tangential flow filter332, as verified by the liquid flow meter 340, the permeate path 334 isclosed by the permeate control valve 342. The control valve 326 can alsobe closed to verify that only the metered initial input volume of liquidis being processed. In this regard, the permeate control valve 342 isopen while the initial volume of liquid is being processed by thetangential flow filter 332 so that liquid stripped of material can beremoved from the system 300, e.g., via the drainage line 330.

Moreover, after a suitable sample (concentrate) has been collected, thepermeate path 334 is closed (e.g., via the permeate control valve 342)and the retentate path 336 is opened. The concentrated liquid, with thecellular material entrained, is flushed out of the tangential flowfilter 332 and into the liquid reservoir 306. The flow rate of thisflush is controlled by the regulated pressure. The volume ofconcentrated liquid flushed from the tangential flow filter 332 iscontrolled by the time the retentate control valve 338 is open.

In certain embodiments, the apparatus can comprise a concentrated liquidreservoir located downstream of the tangential flow filter, and apressure regulator that controls a pressure of the liquid in theconcentration stage, the liquid in the concentration stage operated at ahigher pressure than a pressure of a liquid source.

For instance, in the illustrated embodiment, the reservoir 306 receivesand holds the retentate until the aerosolizing stage 308 initiates anaerosolizing operation. As soon as the flush has completed and theretentate control valve 338 has closed, another concentration stage 304can be initiated, running in parallel with the aerosolizing stage 308.This parallel processing reduces the effective time per sample andallows for the liquid source to be processed close to continuously.

In example embodiments, the aerosolizing stage 308 comprises aperistaltic pump and a nebulizer, and the drying stage 310 comprises adrying chamber. Here, the peristaltic pump may control a flow of theliquid into the nebulizer, which can be at a flow rate substantiallyequal to a drying capacity of the drying chamber. The nebulizer receivesthe liquid and coverts the received liquid into aerosolized liquiddroplets, and the drying chamber receives the aerosolized liquiddroplets and separates cellular material from the droplets. In someembodiments, the peristaltic pump controls the flow of the liquid intothe nebulizer at a flow rate, the flow rate substantially proportionalto a drying capacity of the drying chamber.

In the aerosolizing stage 308, a pump 344 draws the concentrated liquidout of the reservoir 306. The drawn liquid is passed via an aerosolizingcontrol valve 346 through a conduit where the liquid is measured by abubble/air liquid sensor 348, and is injected into a nebulizer 350,e.g., via a micro bore tubing. The nebulizer 350 converts the liquidstream into aerosolized liquid droplets. The droplets pass through adrying chamber 352 of the drying stage 310, and the liquid evaporates,leaving the cells in the airstream. Any cellular material in theconcentrated liquid is thereby separated from the liquid andaerosolized. The aerosolized, separated, and dry cellular material isavailable for analysis or collection.

The aerosolizing pump 344 is selected to control the liquid flow at aflow rate that matches the drying capacity of the aerosol drying chamberof the drying stage 310. By way of example, a rate in the range of 0.01to 0.1 milliliter per minute may be implemented in a practicalimplementation.

The temperature of the drying chamber 352 of the drying stage 310 iscontrolled by a temperature control loop 354, and heaters are attachedto the dryer to elevate its temperature. Makeup air entering the dryercan be heated or dried, as necessary, depending on the environmentaltemperature and humidity. Makeup air entering the dryer is filtered by afilter 356 to ensure that no cellular particles are introduced ascontaminants in the air stream.

After drying, the material is collected at the collection stage 312,e.g., onto the material substrate 314, for transport to an analyzer 360,e.g., analogous to the analyzer 108 described more fully with regard toFIG. 1.

The system 300 includes a controller 370, e.g., a control board runningsoftware needed to automate one or more of the operations describedherein. In some embodiments, the controller 370 also interfaces withanother system, such as the analyzer 360, in order to operatesynchronously with the analyzer 360. Synchronization allows for analysisto also run in parallel with sample preparation, further reducing timeto result. Here, the controller 370 is analogous to the controller 216(FIG. 2) and/or controller 112 (FIG. 1).

More particularly, to facilitate automation, the controller 370 iscontrollably coupled to the various valves, meters, sensors, etc. Forinstance, in the illustrated example, the controller 370 is coupled tothe input control valve 324 to enable fluid to flow into the inputstage. In certain embodiments, controller 370 controls the input controlvalve 324 and other necessary hardware, e.g., pump, pressure regulator,etc., as the application dictates, to input the liquid as a predefinedpressure, which can be set, regulated, etc. via control of thecontroller 370.

To concentrate material, the controller 370 opens the first controlvalve 326, and closes the second control valve 328. This causes fluid toflow into the tangential flow filter 322. The controller 370 can closethe first control valve 326 and open the second control valve 328 todrain any excessive collected fluid, once an acceptable collectionoperation is performed.

In an example implementation, the controller 370 controls the retentatecontrol valve 338 to select one of a closed position, an “open toreservoir” position, and an “open to drain” position. As describedherein, the controller 370 controls the retentate control valve 338 tothe “open to drain” position for operations requiring that the LSA isautomatically primed and cleaned. Using this “open to drain” position,the controller 370 directs liquid through the filter and out to drain330 without passing through the aerosolizing components.

During material collection, the controller 370 controls the retentatecontrol valve 338 to be in a closed position. The controller 370 alsocontrols the permeate control valve 342 to be open. As material iscollected by the tangential flow filter 322, the controller 370 monitorsthe waste liquid via the liquid flow meter 340. The liquid flow meter340 used during the concentration stage quantifies the initial volume.This information is stored by the control software and is available forsubsequent analyses where the material found may need to be quantifiedrelative to the initial volume, e.g., by calculating a cellularconcentration.

Once the controller 370 detects a target, e.g., a predetermined amountof metered liquid via the liquid flow meter 340, after a predeterminedtime period, after a predetermined amount of material is built up in thetangential flow meter, other triggers, combinations thereof, etc., thecontroller 370 closes the permeate control valve 342 and opens theretentate control valve 338 to the second position “open to reservoir”.This allows the low volume, high concentration liquid to flow from thetangential flow filter 322 to the reservoir 306.

The controller 370 closes the retentate control valve 338 once theliquid transfers from the tangential flow filter 322 to the reservoir306. The controller 370 then controls the pump 344 and opens theaerosolizing control valve 346 to draw the concentrated liquid into theaerosolizing stage 308. The controller 370 reads the bubble/air liquidsensor 348 to determine when the fluid is extracted from the reservoir306.

The controller 370 controls the nebulizer 350 to convert the liquid withmaterial entrapped therein, to an aerosol, which allows the liquid to beevaporated by the dryer, and the material to be collected onto thematerial substrate 314. Here, the controller 370 controls thetemperature of the drying stage 310, e.g., via temperature control loop354 and the flow rate from the pump 344, so that the droplets that passthrough the drying chamber 352 of the drying stage 310, evaporateleaving the cells in the airstream, thereby separating the material onto the material substrate.

In some embodiments, the controller 370 may also be coupled todownstream electronics, e.g., to an industrial or pharmaceuticalmanufacturing process that utilizes the liquid. This can be useful toautomate machine start/stop conditions based upon suitability of theliquid.

All components in the LSA are selected to be capable of sterilizationand resistant to microbial contamination. This reduces the risk that theaerosolized sample is contaminated by microbial material containedinside the LSA. For analysis applications, contamination would lead tofalse positives and inaccurate quantification of cellular material.

Moreover, while the above-example implementations have focused onextracting cellular material from the initial volume, other particulatescan be extracted with the LSA. For instance, the tangential flow filtercan be selected to determine what size range of particles are retainedand which are excluded. Also, other non-soluble particles, includingproteins and polymers, can extracted.

Referring to FIG. 4, example select components of a concentration stageare illustrated according to aspects of the present disclosure. Theillustrated concentration stage 404 is referred to herein as a “LiquidSample Concentrator” (LSC), and can be utilized for applicationsanalogous to the concentration stage 304 of FIG. 3. In this regard, theLSC can be used in place of the concentration stage 304, with the othercomponents and features disclosed in FIGS. 1-3. As such, like elementsare illustrated with corresponding reference numerals.

The concentration stage 404 includes first control valve 426 analogousto the first control valve 326 of FIG. 3. The first control valve 426 iscontrolled by the controller (see controller 112, FIG. 1; controller216, FIG. 2; or controller 370, FIG. 3) to open in order to accept avolume of liquid, e.g., on the order of 1 to 100 liters, for processingin an example implementation. In an example embodiment, this “initialvolume” is introduced at an elevated pressure that is regulated by theLSC to be in the range, for instance, of 5 to 30 pounds per square inch.This controlled but elevated pressure provides the motive force for theconcentration stage 404. The LSC regulates the pressure so that theoriginal source of liquid can have variable characteristics, including awide range of pressures and being static or flowing. The liquid may alsoflow through an optional flow restrictor 478 to modify a flow rate ofthe liquid.

For concentrating microorganisms and other particulates in the liquid,the initial volume is directed into a recirculating loop 480. Moreparticularly, the recirculating loop 480 receives, as an input, liquidthrough the first control valve 426. Once input, the liquid is processedby a loop that flows from a concentrator reservoir 482 to a tangentialflow filter 432 (e.g., analogous to the tangential flow filter 332 ofFIG. 3), then to a retentate control valve 438 (analogous to theretentate control valve 338 of FIG. 3), and then back to theconcentrator reservoir 482.

As the recirculating liquid passes through the tangential flow filter432, a fraction of the liquid (but none of the microorganisms) permeatesthe filter and flows to a permeate path 434. The volume of the liquidthat continues circulating is reduced, and the concentration ofmicroorganisms within that volume is increased. The volumetric flow rateof the permeate (e.g., 1 to 3 mL/sec) and the transmembrane pressure ofthe tangential flow filter 432 (e.g., 3 to 15 psi) are selected tooptimize the recovery of microorganisms in the concentrate.Microorganisms may be less likely to be captured by the tangential flowfilter surface, or other loop surfaces, under these flow and pressureconditions. The pressure differential across the filter is controlledusing a second flow restrictor 484.

The inclusion of the concentrator reservoir 482 (which may be vented toan overfill pipe) as part of the recirculation loop 480 enables thesystem to process an arbitrarily large volume in stages. In an exampleimplementation, a liquid sensor 486 at an outlet of the concentratorreservoir 482 is used to automatically detect when the volume in theconcentrator reservoir 482 is low enough to accept additional liquid.The volume of the liquid processed is measured by the flow meter 440 onthe liquid permeate path 434. The controller is programmed with a targetprocess volume and continues refilling the concentrator reservoir 482,and recirculating the concentrated liquid, until that target volume isreached.

Once the controller detects that a defined target is reached, theconcentration stage 404 enters a concentrate transfer mode. The goal ofthe transfer is recovery of all the concentrated liquid. This isachieved by a processes comprising running a recirculation pump 488 inreverse flow, and temporarily placing all the concentrated liquid in theconcentrator reservoir 482. The process also comprises rotating theretentate control valve 438 position to close the recirculation loop andopen the path to the second reservoir (main reservoir) (e.g., seereservoir 306, FIG. 3). Yet further, the process comprises running therecirculation pump 488 in forward flow, transferring the concentratedliquid from the concentrator reservoir 482 to the reservoir 306 (FIG.3), and drawing air into the recirculation loop through a filtered ventof the concentrator reservoir 482 to serve as the “makeup air” and allowall liquid to transfer out of the retentate control valve 438 to themain reservoir (e.g., reservoir 306, FIG. 3).

Notably, the main reservoir (e.g., see 306, FIG. 3) receives and holdsthe concentrated liquid for subsequent transfer to an analysis stage(e.g., analyzer 108, FIG. 1). Because the main reservoir is separatedfrom the recirculation loop 480 by the retentate control valve 438,concentration, transfer, and any subsequent analyses can run inparallel. This parallel processing reduces the effective time persample. In certain embodiments, the concentration stage 404 iscontrolled by a controller running the software needed to automate itsoperation. The controller can interface with another system, such as ananalyzer, to operate synchronously, e.g., as described with reference toFIG. 3. Synchronization allows for analysis to also run in parallel withsample preparation, further reducing time to result.

The flow meter 440 quantifies the volume of processed liquid. Thisinformation is stored by the control software and is available forsubsequent analyses where the material found may need to be quantifiedrelative to the initial volume, e.g., by calculating a cellularconcentration.

All components in the concentrator stage 404 are selected to be capableof sterilization and are preferably resistant to microbial contaminationto reduce the risk that the concentrated sample is contaminated bymicrobial material contained inside the concentrator stage 404. Foranalysis applications, contamination can lead to false positives andinaccurate quantification of cellular material.

In certain embodiments, components in the concentrator stage 404 and theconnectors between them, are selected to exclude “dead” volume, regionsthat fluid can get into and be difficult to get out. Dead volumesencourage bacterial growth, can lead to sample carry over, and can actas reservoirs of unintended chemicals (such as cleaning agents). Certainembodiments here address this issue with a connection of two permeateports on the filter 432. For such a two-port embodiment, in thisconfiguration, some embodiments only connect one of the ports. However,this creates a dead volume at the second port that can cause any of theproblems described above and, thus, an alternative approach is toconnect both permeate ports.

Aspects herein address a potential issue of liquid overflow oroverpressure. The flow restrictor 478 is included to constrain the rateof fluid transfer into the reservoir 482. In the event of a system powerloss, which would stop recirculation but allow for the reservoir 482 tocontinue to fill, this restricted rate is low enough to not exceed thewaste line capacity.

The components that form the recirculating loop are arranged in a mannerthat minimizes the internal volume of that loop. During concentration,the minimum volume of the liquid (and therefore the maximumconcentration of the particles) is determined by the volume of therecirculation loop. Therefore, both the selection of components and thearrangement of those components is used to minimize this volume.

While discussed generally in the context of concentrating microorganismsfrom the liquid, other particulates can be concentrated with theconcentration stage 404. For instance, the filter 432 can be selected todetermine what size range of particles are retained and which areexcluded. Other non-soluble particles, including proteins and polymers,can be automatically extracted.

With reference to FIG. 5, a process 500 for extracting a material from aliquid sample is illustrated. The process 500 may be implemented using,for example, any system, apparatus, components, combination ofcomponents, combinations of features and capabilities, etc., describedwith reference to the FIGURES herein.

An input phase of the process 500 includes introducing at 502, aninitial liquid volume from a liquid source into a concentration stagefor extracting a material from a liquid, examples of which are describedmore fully herein.

The process 500 also comprises directing, at 504, the initial liquidvolume through a tangential flow filter. As set out in greater detailherein, the corresponding apparatus may comprise a plurality of valvesthat cooperate to define multiple paths for the flow of liquid throughthe system. The initial liquid volume follows a first path, e.g., apermeate path, from the tangential flow filter and toward a drain line.The liquid may be introduced into the apparatus at an elevated pressurerelative to the liquid source. After the initial liquid volume haspassed through the tangential flow filter, the tangential flow filtercomprises a concentrated liquid with a smaller liquid volume and ahigher concentration of the material as compared to the initial liquidvolume.

Here, the process optionally comprises directing, at 506, a concentratedliquid into a storage container. For instance, in an exampleimplementation, the concentrated liquid is collected and stored bydirecting the concentrated liquid along a second path, e.g., a retentatepath, and into storage container, e.g., a concentrated liquid reservoir,as described herein. Following collection of the concentrated liquid inthe concentration liquid reservoir, a new concentration phase may beginwith the introduction of a second initial liquid volume at 502.

The aerosolizing phase of the process 500 begins with introducing, at508, e.g., by a peristaltic pump, a portion of the concentrated liquidfrom the concentrated liquid reservoir into an aerosolizing stage, e.g.,which includes a nebulizer. The aerosolizing phase also includesproducing, at 510, aerosolized liquid droplets. For instance, in thenebulizer, the concentrated liquid is vaporized and turned intoaerosolized liquid droplets comprising the material.

The process 500 also comprises a drying stage, which includes heating,at 512, the aerosolized liquid droplets in a drying chamber to separatethe material from the liquid. The liquid in the aerosolized liquiddroplets evaporates, leaving the aerosolized material in the air withinthe drying chamber. The peristaltic pump may control the flow of theconcentrated liquid at a flow rate that substantially matches a dryingcapacity of the drying chamber.

The process 500 can then optionally comprise providing, at 514, anaerosolized material to a processing station(s) for storage and/oranalysis, examples of which are set out in greater detail herein, e.g.,with reference to the analyzer 108 (FIG. 1); analyzer 360 (FIG. 3), etc.

Prior to beginning a new concentration phase, the process 500 maycomprise initiating an optional cleaning cycle, 516, in which a cleaningliquid is directed along a third path, e.g., a drain path, to flush outand clean the components of the system associated with the concentrationphase.

In some implementations, one or more portions of the process 500 may befully or partially automated. For example, as described in greaterdetail herein, a controller may control the introduction and flow ofliquid through the system and the handling of the aerosolized materialproduced by the process 500.

Referring briefly to FIG. 6, an apparatus 600 for extracting materialsfrom liquids is illustrated according to further aspects of the presentdisclosure. Analogous to other embodiments described herein, theapparatus 600 includes a concentration stage 602 that accepts an initialliquid volume having an initial concentration of a material. Theillustrated concentration stage 602 comprises a tangential flow filter604 that accepts the initial liquid volume. Also, the tangential flowfilter collects the material from the initial liquid volume, produces apermeate that is substantially devoid of the collected material, andproduces a retentate having a higher concentration of the material thanthe initial concentration. The concentration stage 602 also includes apermeate path 606 from the tangential flow filter 604, which defines aconduit for the permeate. In this example embodiment, the permeate path606 includes a flow meter 608 and a permeate control valve 610there-along. The concentration stage 602 further includes a retentatepath from the tangential flow filter, which defines a conduit for theretentate, the retentate path 612 comprising a retentate control valve614. An aerosolizing stage 616 is coupled to the retentate path 612. Asdescribed more fully herein, the aerosolizing stage 616 converts theretentate into an aerosol. A drying stage 618 dries the aerosol toextract the material onto a material substrate. A controller 620 iscoupled to the concentration stage (e.g., to the permeate control valve610 and to the retentate control valve 614 to sequence the flow ofoperation in a manner analogous to that described more fully herein. Thecontroller 620 is also coupled to the aerosolizing stage 616, whereinthe controller 620 automates liquid sample collection. An analyzer 622is also coupled to the controller 620, which operates in parallel withthe liquid sample collection to monitor, detect, analyze, etc., thepreviously collected sample.

In this regard, the controller 620 can be coupled to the variouscomponents by coupling to meters, sensors, controllable valves, etc., asdescribed more fully herein. Likewise, the analyzer 622 can implementany combination of monitoring, analyzing, and outputting functions, asdescribed more fully herein.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the disclosure.As used herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof.

The description of the present disclosure has been presented forpurposes of illustration and description, but is not intended to beexhaustive or limited to the disclosure in the form disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of thedisclosure.

Having thus described the disclosure of the present application indetail and by reference to embodiments thereof, it will be apparent thatmodifications and variations are possible without departing from thescope of the disclosure defined in the appended claims.

What is claimed is:
 1. An apparatus that extracts materials fromliquids, the apparatus comprising: a concentration stage that accepts aninitial liquid volume, the initial liquid volume having an initialconcentration of a material, the concentration stage comprising: afilter that accepts the initial liquid volume, collects the materialfrom the initial liquid volume, produces a permeate that issubstantially devoid of the collected material, and produces a retentatethat has a higher concentration of the material than the initialconcentration; a recirculating loop comprising: a concentrator reservoirthat flows to the filter; and a retentate control valve that controlsflow back to the concentrator reservoir; a first path from the filterthat defines a conduit for the permeate; and a second path from thefilter that defines a conduit for the retentate; an aerosolizing stagecoupled to the second path, wherein the aerosolizing stage converts theretentate into an aerosol; and a drying stage that dries the aerosol toextract the material, the extracted material collected onto a materialsubstrate.
 2. The apparatus of claim 1, wherein: the second pathcomprises a retentate control valve; and the first path comprises: aflow meter; and a permeate control valve, wherein the permeate controlvalve is open and the retentate control valve is closed duringcollection of the material.
 3. The apparatus of claim 2, wherein theretentate control valve comprises: a closed position; an open position;and an open to drain position, wherein the open to drain positionprovides a drain path to prime and clean the filter that directs fluidto a drain line and bypasses the aerosolizing stage.
 4. The apparatus ofclaim 3, wherein the drain path directs the liquid through theconcentration stage and into the drain line and does not enter theaerosolizing stage.
 5. The apparatus of claim 1 further comprising: apressure regulator that controls a pressure of the liquid in theconcentration stage, the liquid in the concentration stage operated at ahigher pressure than a pressure of a liquid source.
 6. The apparatus ofclaim 1, wherein: the aerosolizing stage comprises: a peristaltic pump;and a nebulizer; and the drying stage comprises: a drying chamber,wherein: the peristaltic pump controls a flow of the liquid into thenebulizer; the nebulizer receives the liquid and coverts the receivedliquid into aerosolized liquid droplets; and the drying chamber receivesthe aerosolized liquid droplets and separates cellular material from thedroplets.
 7. The apparatus of claim 6, wherein the peristaltic pumpcontrols the flow of the liquid into the nebulizer at a flow rate, theflow rate substantially proportional to a drying capacity of the dryingchamber.
 8. The apparatus of claim 1, further comprising a controllercoupled to the concentration stage, the controller further coupled tothe aerosolizing stage, wherein the controller automates liquid samplecollection.
 9. The apparatus of claim 8, wherein the controller isfurther coupled to an analyzer station, such that liquid samplecollection operates in parallel with the analyzer.
 10. The apparatus ofclaim 1, wherein the filter is a tangential flow filter.
 11. A processfor extracting materials from liquids, the process comprising:introducing an initial liquid volume into a concentration stage, theinitial liquid volume having an initial concentration of a material;directing the initial liquid volume along a permeate path such that aportion of the initial liquid volume flows through a filter and toward adrain line, the filter for entrapping the material to produce aconcentrated liquid, the concentrated liquid having a higherconcentration of the material than the initial concentration; anddirecting the concentrated liquid out of the concentration stage;introducing a portion of the concentrated liquid into an aerosolizingstage comprising a nebulizer to produce aerosolized liquid droplets; andheating the aerosolized liquid droplets in a drying stage comprising adrying chamber to extract the material from the liquid droplets.
 12. Themethod of claim 11 further comprising providing the extracted materialto an analyzer to classify particulates contained within the extractedmaterial.
 13. The method of claim 11 further comprising: directing theconcentrated liquid into a storage container; and introducing a secondliquid volume upon directing the concentrated liquid into the storagecontainer.
 14. The method of claim 11 further comprising controlling apressure of the initial liquid volume upon introducing the initialliquid volume into the concentration stage, the pressure of the initialliquid volume being higher than a pressure of a liquid source.
 15. Themethod of claim 11 further comprising controlling a flow rate of theconcentrated liquid into the nebulizer, the flow rate beingsubstantially proportional to a drying capacity of the drying chamber.16. The method of claim 11, wherein directing a concentrated liquid outof the concentration stage comprises directing the concentrated liquidalong a retentate path into a storage container.
 17. The method of claim16 further comprising initiating a cleaning cycle, the cleaning cyclebeing initiated after directing the concentrated liquid along theretentate path into the storage container, the cleaning cycle furtherbeing initiated prior to introducing a second liquid volume into theconcentration stage.
 18. The method of claim 17, wherein the cleaningcycle comprises directing a cleaning liquid along a drain path when: aselector valve is in an open position; a first control valve is in anopen position; and a second control valve is in a closed position. 19.An apparatus for extracting materials from liquids, the apparatuscomprising: a concentration stage that accepts an initial liquid volume,the initial liquid volume having an initial concentration of a material,the concentration stage comprising: a filter that accepts the initialliquid volume, the filter further collects the material from the initialliquid volume, the filter further produces a permeate that issubstantially devoid of the collected material, the filter furtherproduces a retentate, the retentate having a higher concentration of thematerial than the initial concentration; a permeate path from thefilter, which defines a conduit for the permeate, the permeate pathcomprising: a flow meter; and a permeate control valve; and a retentatepath from the filter, which defines a conduit for the retentate, theretentate path comprising a retentate control valve; an aerosolizingstage coupled to the retentate path, wherein the aerosolizing stageconverts the retentate into an aerosol; a drying stage that dries theaerosol to extract the material, wherein the extracted material iscollected onto a material substrate; a controller coupled to theconcentration stage, the controller further coupled to the aerosolizingstage, wherein the controller automates liquid sample collection; and ananalyzer coupled to the controller, which operates in parallel with theliquid sample collection.